Background: The spermatogenesis system includes highly radiosensitive cells. Hence, this system is a potential target for toxic effects of ionizing radiation during radiotherapy of abdomen and pelvis cancers, as well as after accidental radiation events. Accordingly, metformin and melatonin are two important radioprotectors that have shown an ability to prevent cell death through neutralization of free radicals and stimulating DNA damage responses. Objective: To evaluate the radioprotective effects of melatonin and metformin on mice spermatogenesis when administered alone or as a combination. Materials and Methods: In this histological Study, 40 (6-8 wk, 30 gr) NMRI mice were divided into 8 groups (n = 5/each) as control, metformin, melatonin, melatonin + metformin, radiation, radiation + melatonin, radiation + metformin, and radiation + melatonin + metformin. 37 days after the irradiation, the testicular tissues were collected for histological evaluation. Results: Single administration of melatonin could ameliorate effectively radiation toxicity in mice testis. Metformin showed radioprotective effects on some parameters such as the numbers of spermatogonia and mature sperms. Interestingly, the melatonin and metformin combination reversed the reduced number of sperms rather than single drug administration. Conclusion: The combination of melatonin with metformin can protect mice spermatogenesis against ionizing radiation more effectively compared to the single forms of these drugs. Key words: Radiation, Testis, Leydig cells, Melatonin, Metformin, Spermatogenesis.
Background: ejunum is one of the most radiosensitive parts of the gastrointestinal system. This is the main issue, leading to several side effects to patients with abdominal cancers, in addition to affecting their quality of life. Epithelial layer and clonogenic cells in the jejunum are the most sensitive parts of the intestine, while damage to vascular may lead to chronic inflammation and bleeding. Both melatonin and metformin have shown abilities to attenuate radiation toxicities through the modulation of DNA damage responses, neutralization of free radicals and alleviation of inflammation. In this study, we aimed to evaluate the possible radioprotective effects of melatonin and metformin when administered either alone or as a combination, in rat’s jejunum against a high dose of radiation. Methods: 40 male rats were divided into 8 groups as G1: control; G2: metformin; G3: melatonin; G4: melatonin + metformin; G5: radiation; G6: radiation + melatonin; G7: radiation + metformin; G8: metformin + melatonin + radiation. Rats were irradiated with 10 Gy gamma rays, while treatments were administered at 100 mg/kg. The ratio for melatonin and metformin was 1:1. 3.5 days after irradiation, all rats were sacrificed, followed by histopathological evaluation of the jejunum. Results: This study showed that whole body irradiation of rats led to severe injuries to the epithelial and vascular of jejunum. A single administration of either melatonin or metformin was unable to mitigate radiation toxicity. However, administering the combination of melatonin and metformin could mildly mitigate radiation-induced jejunum injury. Conclusion: From the results of this study, we suggest that the combination of melatonin and metformin has superior radioprotective effect for jejunum compared with the single administration of these drugs.
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